While live bacteria commonly cause infection, the relative role of bacterial toxins versus live bacteria to produce morbidity and mortality is not known, if bacterial toxins are important factors, therapies directed at these toxins may be required. Even if no bacteria remain alive or grow, these preformed toxins may be important in determining morbidity and mortality. Therapies directed at these toxin may be important additions to antibiotic therapy. Using two E. coli in the canine model, we designed a study to determine whether organism virulence factors or bacterial toxins were more important in producing septic shock. Measures of hemodynamic shock, blood cultures, endotoxin levels and survival were done serially with both organisms live, both organisms killed, and with purified endotoxin from these organisms. Approximately 4 man years have gone into this study. Preliminary results from this study have been presented at the American Federation of Clinical Research and the Society of Critical Care Medicine. This presentation won a poster award in 1990. There has been much interest in these data as determination of the factors that produce morbidity in infection will guide trials for future therapies of children and adults with septic shock.